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Titre du document / Document title

Target-driven exploratory study of imatinib mesylate in children with solid malignancies by the Innovative Therapies for Children with Cancer (ITCC) European Consortium

Auteur(s) / Author(s)

Innovative Therapies for Children with Cancer (ITCC) European Consortium
GEOERGER Birgit (1) ; MORLAND Bruce (2) ; NDIAYE Anna (3) ; DOZ Francois (4) ; KALIFA Gabriel (5) ; GEOFFRAY Anne (6) ; PICHON Fabienne (7) ; FRAPPAZ Didier (8) ; CHATELUT Etienne (9) ; OPOLON Paule (10) ; HAIN Sharon (11) ; BODERET Francoise (12) ; BOSQ Jacques (13) ; EMILE Jean-Francois (14) ; LE DELEY Marie-Cecile (3) ; CAPDEVILLE Renaud (15) ; VASSAL Gilles (1) ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

(1) Department of Paediatrics, Institut Gustave Roussy, 39 Rue Camille Desmoulins, University Paris-XI, 94805 Villejuif, FRANCE
(2) Children's Hospital, Steelhouse Lane, B4 6NH Birmingham, ROYAUME-UNI
(3) Biostatistics and Epidemiology, Institut Gustave Roussy, 39 Rue Camille Desmoulins, University Paris-XI, Villejuif, FRANCE
(4) Paediatrics, Institut Curie, 26 Rue d'Ulm, 75248 Paris, FRANCE
(5) CHU Cochin Port Royal, 27 Rue du Faubourg Saint-Jacques, 75014 Paris, FRANCE
(6) CHU Fondation Lenval, 57 Avenue de la Californie, 06000 Nice, FRANCE
(7) Centre Oscar Lambret, 3 Rue Frédéric Combemale, BP 307, 59020 Lille, FRANCE
(8) Centre Léon Bérard, 28 Rue Laennec, 69373 Lyon, FRANCE
(9) EA3035 Institut Claudius-Regaud, 31052 Toulouse, FRANCE
(10) UMR8121 Vectorology and Gene Transfer, Institut Gustave Roussy, 39 Rue Camille Desmoulins, Villejuif, FRANCE
(11) University College Hospital, 235 Euston Road, NW1 2BU London, ROYAUME-UNI
(12) CHU Nantes, 50 Route St Sébastien sur Loire, 44093 Nantes, FRANCE
(13) Pathology Departments, Institut Gustave Roussy, 39 Rue Camille Desmoulins, Villejuif, FRANCE
(14) Department of Pathology, Centre Ambroise Pare, 9 Avenue Charles de Gaulle, 92104 Boulogne, FRANCE
(15) Novartis Pharma AG, Lichtstrasse 35, Basel 4002, SUISSE

Résumé / Abstract

Aim: To explore imatinib efficacy and pharmacokinetics in children and adolescents with refractory/relapsing solid tumours, expressing imatinib-sensitive receptor tyrosine kinases. Methods: Exploratory study on imatinib in tumours expressing, at least, one of the receptors KIT or platelet-derived growth factor receptor (PDGFR). Standard radiological response evaluation, pharmacokinetics, gene mutations and positron emission tomography imaging were assessed. Results: Thirty-six patients (median age: 13.7 years) with brain (12), mesenchymal/bone (14) or other solid tumours, received imatinib 340 mg/m2/d over a total of 255 months. Fifteen tumours expressed KIT in ≥ 30% cells, 19 expressed PDGFRA and 25 expressed PDGFRB. Twenty patients experienced grades 1-2 treatment-related toxicities. Ten patients achieved stable disease; one chordoma had metabolic response. Pharmacokinetic data showed high inter-patient variability (variation coefficient: 44% and 53% for plasma imatinib and CGP 74588 AUCs, respectively). Conclusions: Imatinib was tolerated well, but failed to show efficacy according to standard criteria in paediatric malignancies expressing KIT or PDGFR.

Revue / Journal Title

European journal of cancer    ISSN  0959-8049 

Source / Source

2009, vol. 45, no13, pp. 2342-2351 [10 page(s) (article)] (37 ref.)

Langue / Language

Anglais

Editeur / Publisher

Elsevier, Kidlington, ROYAUME-UNI  (1990) (Revue)

Mots-clés anglais / English Keywords

Tyrosine kinase inhibitor

;

Enzyme inhibitor

;

Enzyme

;

Transferases

;

Cancer

;

Human

;

Antineoplastic agent

;

Cancerology

;

Solid tumor

;

Protein-tyrosine kinase

;

Europe

;

Treatment

;

Malignancy

;

Malignant tumor

;

Child

;

Targeting

;

Imatinib

;

Mots-clés français / French Keywords

Inhibiteur de la tyrosine kinase

;

Inhibiteur enzyme

;

Enzyme

;

Transferases

;

Cancer

;

Homme

;

Enfance

;

STI 571

;

Anticancéreux

;

Cancérologie

;

Tumeur solide

;

Protein-tyrosine kinase

;

Europe

;

Traitement

;

Malignité

;

Tumeur maligne

;

Enfant

;

Ciblage

;

Imatinib

;

Mots-clés espagnols / Spanish Keywords

Inhibidor tyrosine kinase

;

Inhibidor enzima

;

Enzima

;

Transferases

;

Cáncer

;

Hombre

;

Anticanceroso

;

Cancerología

;

Tumor sólido

;

Protein-tyrosine kinase

;

Europa

;

Tratamiento

;

Malignidad

;

Tumor maligno

;

Niño

;

Blancado

;

Imatinib

;

Mots-clés d'auteur / Author Keywords

Tyrosine kinase inhibitors

;

Childhood solid tumours

;

Exploratory study

;

Localisation / Location

INIST-CNRS, Cote INIST : 12648, 35400018811043.0160

Nº notice refdoc (ud4) : 21949221



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